The resurgence in cases of neurologic disease caused by West Nile virus (WNV) in the United States in 2012 came as a surprise to the general public and to many non-arbovirus researchers. Following the introduction of WNV into the US in 1999, the number of human infections rose dramatically, peaking in 2002-03. However, cases declined from 2008-11, and it was unclear if the virus would continue to have a low-level endemic transmission pattern with occasional outbreaks, like the related flavivirus, Saint Louis encephalitis virus, or a more active pattern with annual outbreaks, including occasional years with large epidemics, like Japanese encephalitis virus. The large epidemic in 2012 suggests that the United States can expect periodic outbreaks of West Nile fever and neurologic disease in the coming years. In this paper, we consider the causes of the upsurge in WNV infections during the past year and their implications for future research and disease control measures.